Development and characterization of a predictive microCT-based non-union model in Fischer F344 rats
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ORTHOPAEDIC SURGERY
Development and characterization of a predictive microCT‑based non‑union model in Fischer F344 rats M. Hildebrand1 · M. Herrmann1,2 · F. Gieling1 · D. Gehweiler1 · D. Mischler1 · S. Verrier1 · M. Alini1 · S. Zeiter1 · K. Thompson1 Received: 21 June 2020 / Accepted: 28 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Introduction Non-unions remain a clinical problem and are characterised by the failure to heal after a defined period of time. Current preclinical non-union models apply a wide variety of techniques to diminish intrinsic healing potential deviating from the clinical situation. The aim of this study was to develop and characterise a non-union model in rats using internal plate fixation without the need for additional healing insults, whereby bone healing can be longitudinally assessed using microCT. It was hypothesized that healing/non-unions can be accurately predicted at early time points by microCT. Materials and methods Female, skeletally mature Fischer F344 rats received a 2 mm or 1 mm femoral osteotomy, stabilized with either a 2 mm thick plate or a 1.25 mm thick plate. Healing was monitored by microCT over 14 weeks and histological analysis at euthanasia. The mechanical environment was characterised using finite element (FE) modelling and biomechanical testing. Results The majority of animals receiving the 2 mm thick plate displayed poor healing responses in both the 2 mm and 1 mm defect size groups. Bone and cartilage formation were markedly improved using the 1.25 mm thick plate. MicroCT could accurately predict bone forming capacity at early time points (3–4 weeks). Conclusions The 2 mm thick plating system confers poor healing responses in female Fischer F344 rats, comparable to atrophic non-unions. By reducing plate thickness to increase interfragmentary strain within the defect site healing is improved, leading to borderline healing situations or increased abundance of cartilage tissue present in the defect site with ultimate failure to bridge the defect (hypertrophic non-union). Furthermore, microCT can reliably identify delayed/non-healing animals within 4 weeks, thereby allowing their selective targeting for the testing of novel, clinically relevant treatment strategies in different clinical situations aimed at restoring impaired bone healing. Keywords Fracture healing · Delayed union · Non-union · microCT · Osteotomy
Introduction
S. Zeiter and K. Thompson contributed equally to this manuscript. * K. Thompson [email protected] 1
AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos‑Platz, Switzerland
Present Address: IZKF Research Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Würzburg and Orthopedic Center for Musculoskeletal Research, University of Würzburg, Würzburg, Germany
2
Although the process of long bone fracture repair generally proceeds uneventfully, there exists a small fraction of patients (5–20%) that suffer from healing complications following a fractur
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